Smoke-free legislation and the incidence of paediatric respiratory infections and wheezing/asthma: interrupted time series analyses in the four UK nations

We investigated the association between introduction of smoke-free legislation in the UK (March 2006 for Scotland, April 2007 for Wales and Northern Ireland, and July 2007 for England) and the incidence of respiratory diseases among children. We extracted monthly counts of new diagnoses of wheezing/asthma and RTIs among children aged 0–12 years from all general practices in the Clinical Practice Research Datalink during 1997–2012. Interrupted time series analyses were performed using generalised additive mixed models, adjusting for underlying incidence trends, population size changes, seasonal factors, and pandemic influenza, as appropriate. 366,642 new wheezing/asthma diagnoses and 4,324,789 RTIs were observed over 9,536,003 patient-years. There was no statistically significant change in the incidence of wheezing/asthma after introduction of smoke-free legislation in England (incidence rate ratio (IRR) 0.94, 95% CI 0.81–1.09) or any other UK country (Scotland: IRR 0.99, 95% CI 0.83–1.19; Wales: IRR 1.09, 95% CI 0.89–1.35; Northern Ireland: IRR 0.96, 95% CI 0.76–1.22). Similarly no statistically significant changes in RTI incidence were demonstrated (England: IRR 0.95, 95% CI 0.86–1.06; Scotland: IRR 0.96, 95% CI 0.83–1.11; Wales: IRR 0.97, 95% CI 0.86–1.09; Northern Ireland: IRR 0.90, 95% CI 0.79–1.03). There were no demonstrable reductions in the incidence of paediatric wheezing/asthma or RTIs following introduction of smoke-free legislation in the UK

Determination of quantitative trait loci (QTL) for early maturation in rainbow trout (Oncorhynchus mykiss)

To identify quantitative trait loci (QTL) influencing early maturation (EM) in rainbow trout (Oncorhynchus mykiss), a genome scan was performed using 100 microsatellite loci across 29 linkage groups. Six inter-strain paternal half-sib families using three inter-strain F(1) brothers (approximately 50 progeny in each family) derived from two strains that differ in the propensity for EM were used in the study. Alleles derived from both parental sources were observed to contribute to the expression of EM in the progeny of the brothers. Four genome-wide significant QTL regions (i.e., RT-8, -17, -24, and -30) were observed. EM QTL detected on RT-8 and -24 demonstrated significant and suggestive QTL effects in both male and female progeny. Furthermore, within both male and female full-sib groupings, QTL on RT-8 and -24 were detected in two or more of the five parents used. Significant genome-wide and several strong chromosome-wide QTL for EM localized to different regions in males and females, suggesting some sex-specific control. Namely, QTL detected on RT-13, -15, -21, and -30 were associated with EM only in females, and those on RT-3, -17, and -19 were associated with EM only in males. Within the QTL regions identified, a comparison of syntenic EST markers from the rainbow trout linkage map with the zebrafish (Danio rerio) genome identified several putative candidate genes that may influence EM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10126-008-9098-5) contains supplementary material, which is available to authorized users

Comparative mapping of expressed sequence tags containing microsatellites in rainbow trout (Oncorhynchus mykiss)

BACKGROUND: Comparative genomics, through the integration of genetic maps from species of interest with whole genome sequences of other species, will facilitate the identification of genes affecting phenotypes of interest. The development of microsatellite markers from expressed sequence tags will serve to increase marker densities on current salmonid genetic maps and initiate in silico comparative maps with species whose genomes have been fully sequenced. RESULTS: Eighty-nine polymorphic microsatellite markers were generated for rainbow trout of which at least 74 amplify in other salmonids. Fifty-five have been associated with functional annotation and 30 were mapped on existing genetic maps. Homologous sequences were identified for 20 of the EST containing microsatellites to identify comparative assignments within the tetraodon, mouse, and/or human genomes. CONCLUSION: The addition of microsatellite markers constructed from expressed sequence tag data will facilitate the development of high-density genetic maps for rainbow trout and comparative maps with other salmonids and better studied species

Childhood leukaemia: long-term excess mortality and the proportion ‘cured'

Survival from childhood leukaemia has increased, but the proportion of children cured is unknown. The proportion ‘cured' is defined as the proportion of survivors for whom, as a group, there is no longer excess mortality compared to the general population. Average time to cure is defined as the time since diagnosis at which the excess mortality rate has declined to or below a predetermined small value. Data on children diagnosed with leukaemia during 1971–2000 in Great Britain were used to estimate trends in survival, the proportion cured and the average time to cure. Five-year survival for all types of leukaemia combined rose from 33 to 79% by 2000. The percentage cured rose from 25 to 68% by 1995; it is predicted to increase to 73% for those diagnosed more recently. Average time to cure increased from 12 years (95% confidence interval (CI): 11–14) to 19 years (95% CI: 14–26) for lymphoid leukaemia (average annual increase of 0.3 years; P<0.001), but remained at about 5 years for acute nonlymphoblastic leukaemia. The proportion of children cured of leukaemia has risen dramatically, but the period of excess mortality associated with lymphoid leukaemia has also increased, possibly because of late relapse, secondary malignancy and toxicity from treatment

A first generation BAC-based physical map of the rainbow trout genome

Background: Rainbow trout (Oncorhynchus mykiss) are the most-widely cultivated cold freshwater fish in the world and an important model species for many research areas. Coupling great interest in this species as a research model with the need for genetic improvement of aquaculture production efficiency traits justifies the continued development of genomics research resources. Many quantitative trait loci (QTL) have been identified for production and life-history traits in rainbow trout. A bacterial artificial chromosome (BAC) physical map is needed to facilitate fine mapping of QTL and the selection of positional candidate genes for incorporation in marker-assisted selection (MAS) for improving rainbow trout aquaculture production. This resource will also facilitate efforts to obtain and assemble a whole-genome reference sequence for this species.[br/] Results: The physical map was constructed from DNA fingerprinting of 192,096 BAC clones using the 4-color high-information content fingerprinting (HICF) method. The clones were assembled into physical map contigs using the finger-printing contig (FPC) program. The map is composed of 4,173 contigs and 9,379 singletons. The total number of unique fingerprinting fragments (consensus bands) in contigs is 1,185,157, which corresponds to an estimated physical length of 2.0 Gb. The map assembly was validated by 1) comparison with probe hybridization results and agarose gel fingerprinting contigs; and 2) anchoring large contigs to the microsatellite-based genetic linkage map.[br/] Conclusion: The production and validation of the first BAC physical map of the rainbow trout genome is described in this paper. We are currently integrating this map with the NCCCWA genetic map using more than 200 microsatellites isolated from BAC end sequences and by identifying BACs that harbor more than 300 previously mapped markers. The availability of an integrated physical and genetic map will enable detailed comparative genome analyses, fine mapping of QTL, positional cloning, selection of positional candidate genes for economically important traits and the incorporation of MAS into rainbow trout breeding programs

Exceptionally Preserved Jellyfishes from the Middle Cambrian

Cnidarians represent an early diverging animal group and thus insight into their origin and diversification is key to understanding metazoan evolution. Further, cnidarian jellyfish comprise an important component of modern marine planktonic ecosystems. Here we report on exceptionally preserved cnidarian jellyfish fossils from the Middle Cambrian (∼505 million years old) Marjum Formation of Utah. These are the first described Cambrian jellyfish fossils to display exquisite preservation of soft part anatomy including detailed features of structures interpreted as trailing tentacles and subumbrellar and exumbrellar surfaces. If the interpretation of these preserved characters is correct, their presence is diagnostic of modern jellyfish taxa. These new discoveries may provide insight into the scope of cnidarian diversity shortly after the Cambrian radiation, and would reinforce the notion that important taxonomic components of the modern planktonic realm were in place by the Cambrian period

Estimates of linkage disequilibrium and effective population size in rainbow trout

<p>Abstract</p> <p>Background</p> <p>The use of molecular genetic technologies for broodstock management and selective breeding of aquaculture species is becoming increasingly more common with the continued development of genome tools and reagents. Several laboratories have produced genetic maps for rainbow trout to aid in the identification of loci affecting phenotypes of interest. These maps have resulted in the identification of many quantitative/qualitative trait loci affecting phenotypic variation in traits associated with albinism, disease resistance, temperature tolerance, sex determination, embryonic development rate, spawning date, condition factor and growth. Unfortunately, the elucidation of the precise allelic variation and/or genes underlying phenotypic diversity has yet to be achieved in this species having low marker densities and lacking a whole genome reference sequence. Experimental designs which integrate segregation analyses with linkage disequilibrium (LD) approaches facilitate the discovery of genes affecting important traits. To date the extent of LD has been characterized for humans and several agriculturally important livestock species but not for rainbow trout.</p> <p>Results</p> <p>We observed that the level of LD between syntenic loci decayed rapidly at distances greater than 2 cM which is similar to observations of LD in other agriculturally important species including cattle, sheep, pigs and chickens. However, in some cases significant LD was also observed up to 50 cM. Our estimate of effective population size based on genome wide estimates of LD for the NCCCWA broodstock population was 145, indicating that this population will respond well to high selection intensity. However, the range of effective population size based on individual chromosomes was 75.51 - 203.35, possibly indicating that suites of genes on each chromosome are disproportionately under selection pressures.</p> <p>Conclusions</p> <p>Our results indicate that large numbers of markers, more than are currently available for this species, will be required to enable the use of genome-wide integrated mapping approaches aimed at identifying genes of interest in rainbow trout.</p

Lymphatic mapping and sentinel node biopsy in gynecological cancers: a critical review of the literature

Although it does not have a long history of sentinel node evaluation (SLN) in female genital system cancers, there is a growing number of promising study results, despite the presence of some aspects that need to be considered and developed. It has been most commonly used in vulvar and uterine cervivcal cancer in gynecological oncology. According to these studies, almost all of which are prospective, particularly in cases where Technetium-labeled nanocolloid is used, sentinel node detection rate sensitivity and specificity has been reported to be 100%, except for a few cases. In the studies on cervical cancer, sentinel node detection rates have been reported around 80–86%, a little lower than those in vulva cancer, and negative predictive value has been reported about 99%. It is relatively new in endometrial cancer, where its detection rate varies between 50 and 80%. Studies about vulvar melanoma and vaginal cancers are generally case reports. Although it has not been supported with multicenter randomized and controlled studies including larger case series, study results reported by various centers around the world are harmonious and mutually supportive particularly in vulva cancer, and cervix cancer. Even though it does not seem possible to replace the traditional approaches in these two cancers, it is still a serious alternative for the future. We believe that it is important to increase and support the studies that will strengthen the weaknesses of the method, among which there are detection of micrometastases and increasing detection rates, and render it usable in routine clinical practice

Impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on prescription dug spending for children and adolescents: increasing relevance of health economic evidence

<p>Abstract</p> <p>Background</p> <p>During the last decade, pharmaceutical spending for patients with attention-deficit-hyperactivity disorder (ADHD) has been escalating internationally.</p> <p>Objectives</p> <p>First, to estimate future trends of ADHD-related drug expenditures from the perspectives of the statutory health insurance (SHI; Gesetzliche Krankenversicherung, GKV) in Germany and the National Health Service (NHS) in England, respectively, for children and adolescents age 6 to 18 years. Second, to evaluate the budgetary impact on individual prescribers (child and adolescent psychiatrists and pediatricians treating patients with ADHD) in Germany.</p> <p>Methods</p> <p>A model was developed to predict plausible scenarios of future pharmaceutical expenditures for treatment of ADHD. Model inputs were derived from demographic and epidemiological data, a literature review of past spending trends, and an analysis of new pharmaceutical products in development for ADHD. Only products in clinical development phase III or later were considered. Uncertainty was addressed by way of scenario analysis. For each jurisdiction, five scenarios used different assumptions of future diagnosis prevalence, treatment prevalence, rates of adoption and unit costs of novel drugs, and treatment intensity.</p> <p>Results</p> <p>Annual ADHD pharmacotherapy expenditures for children and adolescents will further increase and may exceed €310 m (D; E: ₤78 m) in 2012 (2002: ~€21.8 m; ~₤7.0 m). During this period, overall drug spending by individual physicians may increase 2.3- to 9.5-fold, resulting from the multiplicative effects of four variables: increased number of diagnosed cases, growing acceptance and intensity of pharmacotherapy, and higher unit costs of novel medications.</p> <p>Discussion</p> <p>Even for an extreme low case scenario, a more than six-fold increase of pharmaceutical spending for children and adolescents is predicted over the decade from 2002 to 2012, from the perspectives of both the NHS in England and the GKV in Germany. This budgetary impact projection represents a partial analysis only because other expenditures are likely to rise as well, for instance those associated with physician services, including diagnosis and psychosocial treatment. Further to this, by definition budgetary impact analyses have little to nothing to say about clinical appropriateness and about value of money.</p> <p>Conclusion</p> <p>Providers of care for children and adolescents with ADHD should anticipate serious challenges related to the cost-effectiveness of interventions.</p